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Repotrectinib (TPX-0005)

Name: Repotrectinib (TPX-0005)
Brand: Selleck Chemicals
SKU: S8583
Rating: 5 (6 reviews)

Catalog No.S8583

For research use only.

Repotrectinib (TPX-0005) is a novel ALK/ROS1/TRK inhibitor with the IC50 values of 1.01 nM for WT ALK, 1.26 nM for ALK(G1202R), and 1.08 nM for ALK(L1196M); also a potent SRC inhibitor (IC50 5.3 nM).

Repotrectinib (TPX-0005) Chemical Structure

CAS No. 1802220-02-5

Selleck's Repotrectinib (TPX-0005) has been cited by 6 Publications

Purity & Quality Control

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ALK Signaling Pathway Map

Biological Activity

Description

Targets

ROS1 ^[2]	Trk receptor ^[2]	WT ALK ^[1] (Cell-free assay)	ALK(L1196M) ^[1] (Cell-free assay)	ALK(G1202R) ^[1] (Cell-free assay)	Click to View More Targets
		1.01 nM	1.08 nM	1.26 nM	Click to View More Targets

In vitro

TPX-0005 is an orally available and potent ATP-competitive inhibitor against ALK, ROS1, TRKA, TRKB and TRKC recombinant kinases and their corresponding clinical resistant mutants. TPX-0005 demonstrates potent anti-proliferative activity in the range of sub-nanomolar to low nanomolar in a number of human cancer cell lines and engineered stable cell lines expressing the targeted oncogenes or their solvent front mutants, accompanied by inhibition of target phosphorylation and concomitant inactivation of downstream effectors such as ERK, AKT and STAT3^[2]. TPX-0005 inhibits H2228 cell migration in a wound healing assay with similar activity to saracatinib. TPX-0005 is able to not only inhibit the wild-type and a broad spectrum of mutant ALKs, but also overcome primary resistance and suppress metastatic features by inhibiting SRC^[1].

Assay

Methods	Test Index	PMID

Western blot	pEGFR / pERK / pAKT / pSTAT3 / pPaxillin / Pyap1 / cleaved caspase-3	29433983
Immunofluorescence	pSTAT3(Y705) / STAT3	29433983

In vivo

In patient derived xenograft tumor models, TPX-0005 treatment results in significant regression of tumors harboring the oncogenic ALK, ROS1 and TRKC fusions. Moreover, in a series of mouse xenograft tumor models, TPX-0005 exhibits marked anti-tumor activity not only in tumors harboring the wildtype oncogenic targets but also in tumors harboring the oncogenes with the solvent front mutations via inhibition of the target phosphorylation^[2].

Protocol (from reference)

References

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight	355.37
Formula	C₁₈H₁₈FN₅O₂
CAS No.	1802220-02-5
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	CC1CNC(=O)C2=C3N=C(C=CN3N=C2)NC(C4=C(O1)C=CC(=C4)F)C

Download Repotrectinib (TPX-0005) SDF

In vivo Formulation Calculator (Clear solution)

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Molarity Calculator

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Dilution Calculator Molecular Weight Calculator

Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03093116	Recruiting	Drug: Oral repotrectinib (TPX-0005)	Locally Advanced Solid Tumors\|Metastatic Solid Tumors	Turning Point Therapeutics Inc.	February 27 2017	Phase 1\|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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